Trypanosoma cruzi, the protozoan that causes Chagas disease, is a major cause of morbidity and mortality in South and Central America, primarily among poor persons. The current international effort to eliminate Chagas disease as a public health problem has two goals: to prevent transmission of the parasite to human beings and to identify and treat the millions of people who are already infected in order to prevent life-threatening sequelae. The last decade has provided a series of potential new tools (specifically, advanced immunology, proteomics, molecular biology / molecular epidemiology, genomics, spatial analysis, simulation models) that have only begun to be applied for the diagnosis, epidemiology and control of parasitic diseases. The main theme of the Peru TMRC Program is to apply new tools and information in a concerted manner to develop novel diagnostic and control methods for Chagas disease which could be applied elsewhere. Two Research Projects and Three Cores compose the Program. The overall aim for Research Project 1 is to compare Chagas transmission patterns in rural and urban communities, using ecologic, epidemiologic, qualitative and spatial analysis methods as well as high-resolution molecular characterization of Trypanosoma cruzi and Triatoma infestans in order to develop strategies for control, and the Overall Aim of Research Project 2 is to address the central diagnostic dilemmas of Chagas disease-efficient population screening, timely identification of antitrypanosomal treatment failures, and early detection of those most likely to progress to severe disease - through optimization of existing assays and development of novel diagnostic tools using genomic and proteomic approaches. The above research components of this application encompass several closely connected studies that focus on the twin goals of the global elimination effort: Improved control through: 1 - A rigorous analysis of the ecology and epidemiology of human Chagas disease and its vector in contrasting rural and peri-urban sites with ongoing vectorial T. cruzi transmission;and 2 - Improved guidance for residual insecticide application and post-applicationsurveillance for re-infestation, especially in peri-urban settings;and Improved tools for diagnosis and treatment: 3 - Novel screening strategies to identify T. crazy-infected children;and 4 -New assays and improved use of existing assays for more effective diagnosis of chronic and congenital infection, and to identify early treatment failures after antitrypanosomal treatment. An administrative core (Core A) and two Scientific Cores (Core B - Immunology / Molecular Biology and Core C- Epidemiology / GIS / Data Management) form the structure of the Program.